人类恶性脑肿瘤中化疗耐药相关基因的表达模式：合理选择抗癌药物的实用知识。

Expression pattern of chemoresistance-related genes in human malignant brain tumors: a working knowledge for proper selection of anticancer drugs.

作者信息

Nagane M, Asai A, Shibui S, Oyama H, Nomura K, Kuchino Y

机构信息

Department of Neurosurgery, National Cancer Center Hospital, Tokyo, Japan.

出版信息

Jpn J Clin Oncol. 1999 Nov;29(11):527-34. doi: 10.1093/jjco/29.11.527.

DOI:10.1093/jjco/29.11.527

PMID:10678554

Abstract

BACKGROUND

In addition to traditional modalities such as surgical intervention and radiotherapy, chemotherapy is a common therapeutic method for human malignant brain tumors. However, the effectiveness of chemotherapy is frequently hampered by cancer cell chemoresistance, resulting in an unsatisfactory outcome. To overcome this disadvantage, the proper selection of efficacious anticancer agents is required.

METHODS

The expression levels of chemoresistance-related genes, MGMT, mdr1, MRP, MTIIA and GST-pi, in 28 surgical specimens of human brain tumors and in 10 human glioma cell lines were examined by Northern blot analysis. In addition, the SD10 values of human glioma cell lines against ACNU, CDDP, ADM and VP16 were estimated by a cell survival assay.

RESULTS

The expression levels of each of the chemoresistance-related genes, except MRP, were generally higher in brain tumors than those in non-neoplastic brain tissues. MGMT expression correlated exclusively with ACNU resistance in all glioma cell lines examined (p = 0.0002). The transcriptional level of mdr1 in the tumor cells correlated with the SD10 values of VCR (p = 0.04) and ADM (p = 0.034). In contrast, the expression levels of MTIIA and GST-pi did not correlate with resistance to any of the drugs tested. A correlation of MRP mRNA expression with multidrug resistance was not apparent in the 10 cell lines tested.

CONCLUSIONS

The data indicate that knowledge of the expression levels of MGMT and mdr1 may be particularly useful for a more rational selection of drugs which are not influenced by these resistance genes and which have improved efficacy against human brain tumors.

摘要

背景

除了手术干预和放疗等传统治疗方式外，化疗是治疗人类恶性脑肿瘤的常用方法。然而，癌细胞的化疗耐药性常常阻碍化疗的效果，导致治疗结果不尽人意。为克服这一缺点，需要正确选择有效的抗癌药物。

方法

采用Northern印迹分析法检测28例人脑肿瘤手术标本及10株人胶质瘤细胞系中与化疗耐药相关基因MGMT、mdr1、MRP、MTIIA和GST - pi的表达水平。此外，通过细胞存活试验评估人胶质瘤细胞系对ACNU、CDDP、ADM和VP16的SD10值。

结果

除MRP外，各化疗耐药相关基因在脑肿瘤中的表达水平普遍高于非肿瘤性脑组织。在所检测的所有胶质瘤细胞系中，MGMT表达仅与对ACNU的耐药性相关（p = 0.0002）。肿瘤细胞中mdr1的转录水平与VCR（p = 0.04）和ADM（p = 0.034）的SD10值相关。相反，MTIIA和GST - pi的表达水平与对所测试的任何药物的耐药性均无相关性。在所测试的10个细胞系中，MRP mRNA表达与多药耐药性之间无明显相关性。